rsync to backup Virtual Machines

I would like to have a frequent rsync backup of my system, data and Virtual Machines too.
Usually I backup system and data with a proper cronjob and/or timeshift, but I wonder what would be the best method to backup Virtual Machines while they are running (I am not even sure if this is possible...)
My setup is Linux Host running Virtualbox and Linux Guest, if this matters.
My idea is basically to run a cronjob to rsync VDI disks on the external HDD.
First of all: can I copy a VDI disk when the disk is in use by the VM? In this case, is the VDI copied live (so in the status at it is at the right moment of the backup) or what?
Also, considering that a VDI file is about 50GB what would be a reasonable crontab frequency to avoid rsync process accumulating one on top of the other (I mean, if I set a 5min frequency the first rsync task will be still running when the next starts and so forth).